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Toxicity for Omacetaxine in CML

Insights From: Javier Pinilla-Ibarz, MD, PhD, Moffitt Cancer Center; Camille N. Abboud, MD, Washington University School of Medicine
Published: Tuesday, Jan 31, 2017


Transcript:

Javier Pinilla-Ibarz, MD, PhD:
Omacetaxine is our current treatment alternative for a patient who has failed or is intolerant to 2 or more TKIs. I had to really discuss that many patients—older patients, mainly, or even younger population of patients—may have intolerance to multiple tyrosine kinases. The tyrosine kinase inhibitors may be associated with multiple side effects that, in some instances, make patients unable to really get these very comfortable oral drugs. In this case of omacetaxine, a drug that we have administered subcutaneously, it is able to be efficacious and, at the same time, is able to really avoid many of the side effects that some of the oral drugs have, so, in some cases, improving the quality of life of our patients.

Camille N. Abboud, MD: The toxicities of omacetaxine are different from those of tyrosine kinase inhibitors and are probably related to the potency of this agent. This drug is a liposomal protein inhibitor, so it affects protein synthesis across the board in many organs. The most common side effect is the pancytopenia, which is lowering of the platelet count or hemoglobin, or white blood cell count. This should be managed very carefully by monitoring frequently, once or twice a week, the blood counts in somebody undergoing treatment, and then adjusting the treatment by either dropping the number of omacetaxine injections or shortening the duration of the cycle from, say, 14 days to 12 or 7 days to adapt to the patient’s pancytopenia.

Other unique side effects of omacetaxine include GI toxicity, mainly diarrhea, as seen in the case of accelerated phase, severe vomiting associated with GI bleeding, and also in rare cases of patients who are prone to develop hyperglycemia on omacetaxine, can cause an increase in the blood sugar.

The GI side effects are usually difficult to manage, but I try to manage those by adjusting the dose of omacetaxine or by using histamine inhibitors. Many times, some of the side effects in these patients that have high basophil count is due to histamine release phenomenon, so I use an antihistamine agent or an antiemetic to try and decrease the vomiting. For the diarrhea, I’ve used antimotility agents to help also manage that.

The use of omacetaxine as a bridge to transplant is an interesting question. Obviously, there are very few studies in that area, but I’ve had personal experience using it in a patient with multiple BCR-ABL kinase mutations and resistance to both nilotinib and dasatinib. In this patient, I used imatinib mesylate, which has intermediate activity inhibiting the kinase in combination with omacetaxine, to obtain a hematologic response that was absent before when I had combined imatinib with decitabine. This is an epigenetic modifier that is useful in AML. In that specific patient, this allowed me to lower his blood counts dramatically and get him ready to proceed to an allogeneic stem cell transplant from his sister, which was already worked up. It also allowed me to use normal conditioning without the reduction of the chemotherapy, and attain full engraftment and chimerism by day 100.

Transcript Edited for Clarity
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Transcript:

Javier Pinilla-Ibarz, MD, PhD:
Omacetaxine is our current treatment alternative for a patient who has failed or is intolerant to 2 or more TKIs. I had to really discuss that many patients—older patients, mainly, or even younger population of patients—may have intolerance to multiple tyrosine kinases. The tyrosine kinase inhibitors may be associated with multiple side effects that, in some instances, make patients unable to really get these very comfortable oral drugs. In this case of omacetaxine, a drug that we have administered subcutaneously, it is able to be efficacious and, at the same time, is able to really avoid many of the side effects that some of the oral drugs have, so, in some cases, improving the quality of life of our patients.

Camille N. Abboud, MD: The toxicities of omacetaxine are different from those of tyrosine kinase inhibitors and are probably related to the potency of this agent. This drug is a liposomal protein inhibitor, so it affects protein synthesis across the board in many organs. The most common side effect is the pancytopenia, which is lowering of the platelet count or hemoglobin, or white blood cell count. This should be managed very carefully by monitoring frequently, once or twice a week, the blood counts in somebody undergoing treatment, and then adjusting the treatment by either dropping the number of omacetaxine injections or shortening the duration of the cycle from, say, 14 days to 12 or 7 days to adapt to the patient’s pancytopenia.

Other unique side effects of omacetaxine include GI toxicity, mainly diarrhea, as seen in the case of accelerated phase, severe vomiting associated with GI bleeding, and also in rare cases of patients who are prone to develop hyperglycemia on omacetaxine, can cause an increase in the blood sugar.

The GI side effects are usually difficult to manage, but I try to manage those by adjusting the dose of omacetaxine or by using histamine inhibitors. Many times, some of the side effects in these patients that have high basophil count is due to histamine release phenomenon, so I use an antihistamine agent or an antiemetic to try and decrease the vomiting. For the diarrhea, I’ve used antimotility agents to help also manage that.

The use of omacetaxine as a bridge to transplant is an interesting question. Obviously, there are very few studies in that area, but I’ve had personal experience using it in a patient with multiple BCR-ABL kinase mutations and resistance to both nilotinib and dasatinib. In this patient, I used imatinib mesylate, which has intermediate activity inhibiting the kinase in combination with omacetaxine, to obtain a hematologic response that was absent before when I had combined imatinib with decitabine. This is an epigenetic modifier that is useful in AML. In that specific patient, this allowed me to lower his blood counts dramatically and get him ready to proceed to an allogeneic stem cell transplant from his sister, which was already worked up. It also allowed me to use normal conditioning without the reduction of the chemotherapy, and attain full engraftment and chimerism by day 100.

Transcript Edited for Clarity
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